NAXE

NAD(P)HX epimerase

Basic information

Region (hg38): 1:156591756-156609507

Previous symbols: [ "APOA1BP" ]

Links

ENSG00000163382 ∙ NCBI:128240 ∙ OMIM:608862 ∙ HGNC:18453 ∙ Uniprot:Q8NCW5 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Leigh syndrome (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Early-onset progressive encephalopathy with brain edema and/or leukoencephalopathy (PEBEL)	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Biochemical; Neurologic	27122014; 27616477

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NAXE gene.

• Encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, 1 (5 variants)
• not provided (3 variants)
• Encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NAXE gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	16	2	19
missense	1	1	51	6	5	64
nonsense	4	2	1	3		10
start loss			1			1
frameshift	2		2			4
inframe indel	1		1			2
splice donor/acceptor (+/-2bp)						0
splice region			3	4	1	8
non coding			24	9	16	49
Total	8	3	81	34	23

Highest pathogenic variant AF is 0.0000525

Variants in NAXE

This is a list of pathogenic ClinVar variants found in the NAXE region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-156591765-G-GGGGCCGGGCC			Benign (May 10, 2021)
1-156591765-G-GGGGTCGGGCC			Benign (May 10, 2021)
1-156591765-G-GGGGCCGGGCCGGGCC			Benign (May 14, 2021)
1-156591805-A-G			Uncertain significance (Mar 17, 2022)
1-156591809-C-T			Uncertain significance (Nov 27, 2023)
1-156591821-CGCTGCTGGGCCTCGG-C			Uncertain significance (Jul 19, 2022)
1-156591824-T-C			Uncertain significance (Aug 28, 2023)
1-156591826-C-T			Likely benign (May 05, 2023)
1-156591827-T-C		Inborn genetic diseases	Uncertain significance (Jul 09, 2021)
1-156591831-C-T			Likely benign (Oct 16, 2023)
1-156591858-CG-TC			Likely benign (Mar 23, 2022)
1-156591859-G-C		Encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, 1	Benign (Feb 01, 2024)
1-156591861-G-A			Likely benign (Jun 28, 2022)
1-156591863-C-A			Uncertain significance (May 17, 2022)
1-156591865-C-T			Uncertain significance (Oct 13, 2023)
1-156591875-G-A			Uncertain significance (Jan 02, 2024)
1-156591877-C-T		NAXE-related disorder	Likely pathogenic (Mar 04, 2023)
1-156591912-G-T			Uncertain significance (Feb 18, 2022)
1-156591917-C-T			Uncertain significance (Sep 27, 2022)
1-156591932-C-A		Encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, 1	Pathogenic (Nov 16, 2023)
1-156591968-C-T			Uncertain significance (Jul 17, 2023)
1-156591969-G-A			Benign (Oct 29, 2023)
1-156591970-G-C			Uncertain significance (Mar 22, 2022)
1-156591978-G-A			Likely benign (Jun 17, 2022)
1-156591981-C-A		Encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy	Pathogenic (Nov 14, 2016)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NAXE	protein_coding	protein_coding	ENST00000368235	6	2538

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000244	0.511	125699	0	49	125748	0.000195

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.606	150	172	0.870	0.00000893	1837
Missense in Polyphen		39	63.016	0.61889		699
Synonymous	0.124	73	74.4	0.982	0.00000408	604
Loss of Function	0.746	10	12.9	0.776	5.94e-7	146

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000297	0.000297
Ashkenazi Jewish	0.00	0.00
East Asian	0.000272	0.000272
Finnish	0.0000936	0.0000924
European (Non-Finnish)	0.000241	0.000237
Middle Eastern	0.000272	0.000272
South Asian	0.000196	0.000196
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes the epimerization of the S- and R-forms of NAD(P)HX, a damaged form of NAD(P)H that is a result of enzymatic or heat-dependent hydration. This is a prerequisite for the S- specific NAD(P)H-hydrate dehydratase to allow the repair of both epimers of NAD(P)HX. {ECO:0000255|HAMAP-Rule:MF_03159, ECO:0000269|PubMed:27616477}.
• Disease: DISEASE: Encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy (PEBEL) [MIM:617186]: An autosomal recessive severe neurometabolic disorder characterized by severe leukoencephalopathy usually associated with a trivial febrile illness. Affected infants tend to show normal early development followed by acute psychomotor regression with ataxia, hypotonia, respiratory insufficiency, and seizures. Disease course is rapidly progressive, leading to coma, global brain atrophy, and death in the first years of life. Brain imaging shows multiple abnormalities, including brain edema and signal abnormalities in the cortical and subcortical regions. {ECO:0000269|PubMed:27122014, ECO:0000269|PubMed:27616477}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Metabolism;Nicotinamide salvaging;Nicotinate metabolism;Metabolism of water-soluble vitamins and cofactors;Metabolism of vitamins and cofactors;NADH repair (Consensus)

Recessive Scores

• pRec: 0.0857

Intolerance Scores

• rvis_EVS: -0.4
• rvis_percentile_EVS: 26.53

Haploinsufficiency Scores

• pHI: 0.387
• hipred: N
• hipred_score: 0.301
• ghis: 0.528

Essentials

• essential_gene_gene_trap: N

Mouse Genome Informatics

• Gene name: Naxe

Zebrafish Information Network

• Gene name: naxe
• Affected structure: hepatocyte
• Phenotype tag: abnormal
• Phenotype quality: ballooning

Gene ontology

• Biological process: NAD biosynthesis via nicotinamide riboside salvage pathway;nicotinamide nucleotide metabolic process;protein homotetramerization
• Cellular component: extracellular region;extracellular space;nucleoplasm;mitochondrion;mitochondrial matrix;cytosol;cilium;intracellular membrane-bounded organelle;cell body;extracellular exosome
• Molecular function: nucleotide binding;protein binding;protein homodimerization activity;metal ion binding;NADHX epimerase activity;NADPHX epimerase activity